This project continues to be a multidisciplinary approach to the investigation of various forms of experimental hypertension. The models of hypertension being studied are adrenal-regeneration hypertension, androgen-induced hypertension and the spontaneously-hypertensive rat. The first two of these involve adrenal cortical dysfunction and the studies carried out include the analysis of the various enzyme systems involved in corticosteroidogenesis in the rat adrenal cortex. The methodology which has been developed allows for the analysis of the various cytochrome P-450 systems of adrenal cortical mitochondria and specifically relates the activity of cholesterol side chain cleavage to that of steroid 11 beta and 18-hydroxylation. Concurrent with the in vitro studies, measurement of peripheral plasma levels of corticosterone, 18-hydroxy-DOC and DOC are carried out by sensitive radioimmunoassays and are being used to identify significant disturbances in adrenal cortical function which may result in excess mineralocorticoid secretion and, in turn, hypertension. Adrenal cortical function is also being investigated in the SHR form of experimental hypertension with a search being made for subtle alterations in function as expressed in changes in mineralocorticoid/glucocortical ratios. A significant aspect of the studies involves correlating altered adrenal cortical function with the ultrastructure of the various zones of the adrenal cortex.